Objective:

To evaluate the efficacy and safety of baloxavir combined with neuraminidase inhibitors (NAIs) in hospitalized high-risk patients with severe influenza, focusing on clinical outcomes and adverse events.

Key Findings:

• No significant difference in median TTCI between dual antiviral (baloxavir + NAI) and mono antiviral (NAI alone) groups (P = .48), indicating similar recovery times.
• In patients infected with influenza A H3N2, the dual group had a significantly shorter TTCI (P = .013), suggesting potential benefits in this subgroup.
• Dual antiviral group showed lower mortality (2.17% vs 11.76%, P = .02), indicating a significant reduction in death rates.
• Shorter time to cessation of viral shedding in the dual group (P < .001), highlighting improved virological outcomes.
• Greater reduction in virus titer from baseline to day 2 in the dual group (P < .001), emphasizing the effectiveness of the combination treatment.
• Serious adverse events were comparable between both groups (P = .42), suggesting safety in the combination therapy.

Interpretation:

Combining baloxavir with NAIs may reduce mortality and improve virological outcomes in high-risk patients with severe influenza, particularly in cases of influenza A H3N2, without increasing adverse events, though the findings should be interpreted with caution due to the nature of the post hoc analysis.

Limitations:

• Post hoc analysis may introduce bias and limit generalizability, particularly due to the small sample size for the dual antiviral group, which may affect the robustness of the findings.
• The sample size for the dual antiviral group was relatively small, which may limit the statistical power and reliability of the results.

Conclusion:

The combination of baloxavir and NAIs demonstrates potential benefits in reducing mortality and improving clinical outcomes in high-risk hospitalized patients with severe influenza, warranting further investigation.